An exploration of aptamer internalization mechanisms and their applications in drug delivery

Introduction: As ‘chemical antibodies’, aptamers have some advantages, such as lack of immunogenicity, rapid tissue penetration, cell internalization and so on. Consequently, more and more aptamers have been screened out by the systematic evolution of ligands through exponential enrichment for the desired cells or membrane receptors. On the basis of the result, researchers use aptamers to guide drug targeting to the desired cells and internalization in vivo.

Areas covered: In this review, we explore the mechanisms of cargo- or aptamer-mediated internalization, and then briefly summarize five strategies for exploring the mechanism of aptamer internalization. Finally, we focus on four types of applications involving aptamer internalization: aptamers as drugs, aptamers as chemical drug-delivery systems, aptamer-based chimeras and aptamer-conjugated nanoparticles or block copolymer micelles.

Expert opinion: Two aptamer-internalization mechanisms are known, namely receptor-mediated endocytosis and macropinocytosis. The latter mechanism, which is has only been verified in the internalization of nucleolin aptamer shuttles between the nucleus and cytoplasm, may be important for nuclear internalization and cargo molecule escape from the endosomal compartment. Thus, it is feasible to use some strategies to further explore the macropinocytosis internalization mechanism and then to screen for aptamers similar to the nucleolin aptamer for use with the desired cell types as a targeted delivery tool.